CD4+ T cells can be segregated into distinct subsets based on their pattern of cytokine production. CD4+ T cells that secrete IFN-g are termed Th1 cells while cells that secrete IL-4, IL-5 and IL-13 are termed Th2 cells. While Th1 cells are essential in mediating protection against a variety of intracellular infections they also mediate pro-inflammatory responses associated with a variety of autoimmune diseases. Th2 cells have a role in counter-regulating Th1 responses and are associated with allergic and asthmatic disease. These studies examine the factors, which regulate how T helper responses are sustained in vivo. Recent work explores the mechanism by which CD4+/IFN-g effector cells die in vivo. The work studies the capacity of distinct lineages of Th1 cells to survive in vivo following antigenic stimulation. Populations of Th1 cells which differ in their ability to secrete IL-2 and IFN-g are studied. A major emphasis is to understand differences in how these populations of cells are regulated in vivo. The studies over the past year have shown the following:[unreadable] [unreadable] 1. Th1 effector cells are killed in vivo in an IFN-g dependent manner.[unreadable] 2. IFN-g mediates death of Th1 effector cells indirectly and not in an autocrine manner.[unreadable] 3. Th1 cells have a linear transition from effector cells secreting IFN-g and IL-2 to IFN-g only and then death.